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Alcohol intake, genes responsible for alcohol metabolism, and risk of breast cancer in the PLCO cohort

Principal Investigator
Name
Catherine McCarty
Degrees
-
Institution
Marshfield Clinic Research Foundation
Position Title
-
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
2005-0027
Initial CDAS Request Approval
Apr 21, 2006
Title
Alcohol intake, genes responsible for alcohol metabolism, and risk of breast cancer in the PLCO cohort
Summary
Previous studies and data from PLCO indicate an increased risk of breast cancer with increasing alcohol intake. We propose to conduct a nested case control study within PLCO to describe the influence of polymorphisms in selected alcohol metabolism genes on breast cancer incidence. The interaction of these polymorphisms with alcohol intake and gene-gene interaction and breast cancer risk will also be investigated. Specifically, we will utilize the previously selected 1141 breast cancer cases and 1141 matched controls for whom baseline information, DQx data, and T0 DNA are available. Cases and controls will be genotyped for known polymorphisms in the three genes involved in alcohol metabolism - alcohol dehydrogenase, aldehyde dehydrogenase and CYP2E1. Statistical analyses will be stratified by level of alcohol intake. Logistic regression analyses will be employed to quantify the relationship of genotype to breast cancer incidence.
Aims

The overall goal of this project is to examine the relationship between genes involved in the alcohol metabolism pathway, alcohol intake, and gene-environment interaction on the risk of developing breast cancer in post-menopausal women in PLCO. Primary hypotheses to be tested: 1. Polymorphisms in the alcohol dehydrogenase gene are associated with altered risk of breast cancer. 2. Polymorphisms in the aldehyde dehydrogenase gene are associated with altered risk of breast cancer. 3. Polymorphisms in the CYP2E1 gene are associated with altered risk of breast cancer. 4. Gene-gene interaction between alcohol and aldehyde dehydrogenase genotypes, and CYP2E1 genotype modify risk of breast cancer. 5. Gene-environment interactions between alcohol and aldehyde dehydrogenase genotypes, CYP2E1 genotype and alcohol intake modify risk of breast cancer.

Collaborators

Robert Hoover (NCI, DCEG)
Catherine McCarty (Marshfield Clinic)
Douglas Reding (Marshfield Clinc)
Regina Ziegler (NCI, DCEG)

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